Delving into the Latest Updates on Foscenvivint with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

CTNNB1

Mechanism

CTNNB1 inhibitors(Catenin beta 1 inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication

Liver Cirrhosis

Inactive Indication

Acidemia, IsovalericAcute Myeloid LeukemiaAdenocarcinoma of large intestine+ [11]

Originator Organization

PRISM BioLab Co., Ltd.

Active Organization

Tokyo Metropolitan Komagome Hospital

Inactive Organization

PRISM BioLab Co., Ltd.

Ohara Pharmaceutical Co., Ltd.PRISM Pharma Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC33H35N6O7P

InChIKeyVHOZWHQPEJGPCC-AZXNYEMZSA-N

CAS Registry1422253-38-0

BACKGROUNDIndocyanine green (ICG) is widely used to stain the epiretinal membranes and internal limiting membranes during the pars plana vitrectomy (PPV). This study aims to evaluate the effect of ICG on rat retinas and various retinal cell lines, including ARPE-19 cells, rMC-1 cells, BV2 cells, HRMECs and R28 cells.METHODSICG solutions were prepared and diluted with glucose solution (GS) according to the standard clinical protocols. The retinal cell lines, including ARPE-19 cells, rMC-1 cells, BV2 cells, HRMECs and R28 cells, were treated with the following solutions: normal glucose (NG, 5 mM), GS-1 (92.5 mM glucose), GS-2 (185.02 mM glucose), ICG-1 (92.5 mM glucose + 0.43 mM ICG), or ICG-2 (185.02 mM glucose + 0.86 mM ICG) for durations of 15 or 30 min. In vivo, the right eyes of the rats were intravitreally injected with ICG-1 or ICG-2 (2 μL), while the left eyes were intravitreally injected with GS-1 or GS-2, served as the osmotic controls, for 30 min or 60 min. The rats intravitreally injected with an equivalent volume of NG or 1x phosphate-buffered saline (1x PBS) were served as the normal control or vehicle control. The cell viability was measured with the Cell Counting Kit-8 (CCK-8), while the cell death in retinal cryosections was detected with the TUNEL assay.RESULTSThe viabilities of the different retinal cell lines involved in this study were significantly reduced by both ICG-1 and ICG-2 treatments at both time points, with ICG-2 resulting in lower cell viability compared to the NG group and the osmotic control group. Additionally, GS-2 treatment also exhibited a decrease in retinal cell viabilities in vitro. To further confirm these results, intravitreal injection of ICG or GS induced more apoptotic cell death in rat retinas as evidenced by the TUNEL assay.CONCLUSIONSThe exposure of ICG or its solvent leads to an augmented retinal cell death, which is directly proportional to the concentration and duration of exposure, both in vivo and in vitro. Caution should be exercised during vitrectomy procedures involving ICG administration during clinical practice. It is recommended to advocate for lower concentrations of ICG with reduced exposure time during ocular surgeries.

01 Dec 2024·Neurochemistry International

The wnt/pyruvate kinase, muscle axis plays an essential role in the differentiation of mouse neuroblastoma cells

Article

Author: Mu, Lili ; Wang, Jinghua ; Li, Xinrong ; Wang, Zhenhai ; Zhang, Xiaoyu ; Kong, Qingfei ; Lei, Cheng ; Ge, Xuemin ; Wang, Jiaqi ; Zhao, Wei ; Li, Hulun ; Sun, Shanshan ; Ma, Mingyu ; Jiang, Wei

Neuronal differentiation and neurite growth are essential processes in nervous system development and are regulated by several factors. Although all-trans retinoic acid (ATRA) has been shown to mediate the differentiation of mouse neuroblastoma cells via the activation of several pathways, including Wnt/β-catenin signaling, the mechanism remains unclear. The pyruvate kinase, muscle (PKM) plays an important role in the glycolysis of neuroblastoma cells and regulates the Wnt signaling pathway in various cancer cells. In this study, we hypothesized that the Wnt/PKM axis regulates the differentiation of neuroblastoma cells (Neuro-2a and N1E-115). To test this hypothesis, we used inhibitors and activators of the Wnt/β-catenin and glycolytic pathways in ATRA-induced differentiated Neuro-2a and N1E-115 cells and established cell lines with silenced or a mutant replacement of Pkm. Western blot and qPCR showed that ATRA treatment activated the Wnt signaling pathway and inhibited PKM-mediated glycolysis. The oxygen consumption rate (indicating oxidative phosphorylation) significantly increased, whereas the extracellular acidification rate (indicating glycolysis) significantly decreased during differentiation; these effects were reversed upon PKM inhibition. The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression. Treatment with the Wnt activator kenpaullone promoted Neuro-2a and N1E-115 differentiation, which was reversed by ML-265 administration. These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation.

01 Nov 2024·Experimental Eye Research

Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy

Article

Author: Li, Ziwen ; Cai, Jiping ; Zong, Tianyi ; Zhuang, Miao ; Wang, Xiaolu ; Wang, Yan ; Mu, Tong ; Yao, Yong ; Wu, Meili ; Yang, Qian ; Tan, Chengye ; Xie, Tianhua

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-β2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-β2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and β-catenin in the PVR membranes. ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

100 Deals associated with Foscenvivint

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15034

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 3	US	PRISM BioLab Co., Ltd.	-
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 3	US	PRISM BioLab Co., Ltd.	-
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 3	US	PRISM BioLab Co., Ltd.	-
Liver Cirrhosis	Phase 1	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018
Acidemia, Isovaleric	Phase 1	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Adenocarcinoma of large intestine	Phase 1	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Metastatic Colorectal Carcinoma	Phase 1	US	PRISM Pharma Co., Ltd.	01 Nov 2015
Acute Myeloid Leukemia	Phase 1	US	PRISM BioLab Co., Ltd.	-
Hepatitis B	Discovery	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018
Hepatitis C	Discovery	JP	Ohara Pharmaceutical Co., Ltd.	24 Jul 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04047160 (Pubmed) Manual	Phase 1	Primary Biliary Cholangitis	7	OP-724	(kbcxojsgcq) = nohhtzdzkk jtoswerhyq (rxahccvikh ) View more	Positive	01 Nov 2022
NCT03620474 (Pubmed) Manual	Phase 1/2	Liver Cirrhosis	27	PRI-724 (phase 1)	-	Positive	20 May 2022
NCT03620474 (Pubmed) Manual	Phase 1/2	Liver Cirrhosis	27	PRI-724 (phase 2a)	(vyfihcbxyr) = ntoiibyypd npjgnwtvnb (udjdzmfigk ) View more	Positive	20 May 2022
NCT01764477 (ASCO2016) Manual	Phase 1	Advanced Pancreatic Adenocarcinoma Second line	20	gemcitabine+PRI-724	(wcknrdumdj) = none wnfmserbps (vjtghmqixn ) View more	Positive	03 Jun 2016
NCT01764477 (ASCO2015)	Phase 1	Advanced Pancreatic Adenocarcinoma Second line	10	PRI-724	(yqriexbwif) = zqcxeplqla qsbotycshi (xdznssrsvr )	-	20 May 2015
NCT01302405 (ASCO2013)	Phase 1	HR-positive/HER2-low Solid Tumors	18	PRI-724	(xqnrljrruz) = jtfnygwpwg brphprghfu (ydokclhnal ) View more	-	20 May 2013
ASTRO	Not Applicable	Glioblastoma	-	ICG-001	tgaclemgoy(lnsjqlfhts) = galinhojtq qboknlqwag (lllmtaltuz )	-	01 Nov 2012
ASTRO	Not Applicable	Glioblastoma	-	ICG-001 (Radiation)	gvjtynirtc(swpejtncdq) = lylxkultrx mddtrzpkwn (olesgzvekh )	-	01 Nov 2012